Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects.
Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection and cause of secondary bloodstream infections. Despite many advances in diagnosis, prevention and treatment, CAUTI remains a severe healthcare burden, and antibiotic resistance rates are alarmingly high. In this review, current CAUTI management paradigms and challenges are discussed, followed by future prospects as they relate to the diagnosis, prevention, and treatment. Clinical and translational evidence will be evaluated, as will key basic science studies that underlie preventive and therapeutic approaches. Novel diagnostic strategies and treatment decision aids under development will decrease the time to diagnosis and improve antibiotic accuracy and stewardship. These include several classes of biomarkers often coupled with artificial intelligence algorithms, cell-free DNA, and others. New preventive strategies including catheter coatings and materials, vaccination, and bacterial interference are being developed and investigated. The antibiotic pipeline remains insufficient, and new strategies for the identification of new classes of antibiotics, and rational design of small molecule inhibitor alternatives, are under development for CAUTI treatment.


[Molecular hybridization of native and modified subunits of lactate dehydrogenase isoenzymes and aldolase A in rats].
Experimental conditions for the molecular hybridization in vitro between iodine and native subunits of isoenzymes 1 and 5 of lactate dehydrogenase (LDH) are described. It is also shown that the covalently fixed on the polyacrylamide beads rat J125 labelled LDH-5 and J125 labelled aldolase A, under conditions of complete dissociation of the quaternary structure of these enzymes, only one of the four subunits remain bound with the beads. Subunit of LDH-5, which is covalently bound with the polyacrylamide beads, is capable to hybridize (reassociated) with 3 native subunits. In addition, the immobilized LDH-5 subunits and aldolase A are capable to hybridize with J125 labelled subunits of these enzymes. Thus, when thyrosine, lysine and N-terminal amino acids are modified, subunits of LDH-5 and aldolase A retain their capacity to restore their quaternary structures.


Fast optical switching via stimulated Raman adiabatic passage.
We demonstrate a new approach to fast optical switching with a technique based on stimulated Raman adiabatic passage in which a laser pulse switches the probe field on and off via another coupling pulse. This new kind of optical switching is not limited by the decay rate of an excited state and can operate in the subnanosecond time domain. The experimental observation in Rb atomic vapor is in good agreement with numerical simulations.


Leishmania infantum proteophosphoglycans regurgitated by the bite of its natural sand fly vector, Lutzomyia longipalpis, promote parasite establishment in mouse skin and skin-distant tissues.
We demonstrate that a proteophosphoglycan-rich gel secreted by Leishmania infantum inside the midgut of Lutzomyia longipalpis sand flies (promastigote secretory gel) is regurgitated along with an average dose of 500 L. infantum metacyclic promastigotes per infected bite. Using both low (10³) and high (10⁵) doses of parasites in the ears of BALB/c mice we show that the infections benefit from the presence of vector saliva and parasite gel in the skin. However, chronic infection of the spleen was only enhanced in high dose co-infections with gel. These results provide the framework for a more natural experimental model of visceral leishmaniasis.


Acute care.
What is 'acute care' in Australian general practice? It depends on who you ask. When I use 'acute care' to describe a proportion of my work at an outer suburban Melbourne clinic, I am likely to mean something quite different to a doctor in a regional, rural or remote practice.


A rat model of bone cancer pain.
This study describes the first known model of bone cancer pain in the rat. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed behavioural signs indicative of pain, including: mechanical allodynia, difference of weight bearing between hind paws and mechanical hyperalgesia. The development of the bone tumour and structural damage to the bone was monitored by radiological analysis, quantitative measurement of mineral content and histology. Intra-tibial injections of 3 x 10(3) or 3 x 10(4) syngeneic MRMT-1 cells produced a rapidly expanding tumour within the boundaries of the tibia, causing severe remodelling of the bone. Radiographs showed extensive damage to the cortical bone and the trabeculae by day 10-14 after inoculation of 3 x 10(3) MRMT-1 cells, and by day 20, the damage was threatening the integrity of the tibial bone. While both mineral content and mineral density decreased significantly in the cancerous bone, osteoclast numbers in the peritumoural compact bone remained unchanged. However, tartarate-resistant acid phosphatase staining revealed a large number of polykariotic cells, resembling those of osteoclasts within the tumour. No tumour growth was observed after the injection of heat-killed MRMT-1 cells. Intra-tibial injections of 3 x 10(3) or 3 x 10(4) MRMT-1 cells, heat-killed cells or vehicle did not show changes in body weight and core temperature over 19-20 days. The general activity of animals after injection with live or heat-killed MRMT-1 cells was higher than that of the control group, however, the activity of the MRMT-1 treated group declined during the progress of the disease. Rats receiving intra-tibial injections of MRMT-1 cells displayed the gradual development of mechanical allodynia and mechanical hyperalgesia/reduced weight bearing on the affected limb, beginning on day 12-14 or 10-12 following injection of 3 x 10(3) or 3 x 10(4) cells, respectively. These symptoms were not observed in rats receiving heat-killed cells or vehicle. Behavioural data suggest a reasonable time window for evaluation of anti-nociceptive agents between day 14 and 20 after cancer cell inoculation in this model. Acute treatment with morphine (1-3mg/kg, subcutanously (s.c.)) produced a dose-dependent reduction in the response frequency of hind paw withdrawal to von Frey filament stimulation 17 or 19 days following intra-tibial injections of 3 x 10(3) MRMT-1 cells. A significant reduction in the difference in hind limb weight bearing was also observed. Acute treatment with celebrex (10-30 mg/kg, s.c.) did not affect mechanical allodynia or difference in weight bearing in rats 20 days following treatment with 3 x 10(3) MRMT-1 cells. Although the pathophysiology of cancer pain is largely unknown, significant enhancement of glial fibrillary acidic protein (GFAP) staining in the corresponding segments of the ipsilateral spinal cord highlights the possible involvement of astrocytes. In summary, the induction of bone cancer in the rat by the syngeneic MRMT-1 mammary tumour cell line provides a valid pre-clinical model for pain associated with bone metastases. Significant mechanical hyperalgesia and allodynia develops in association with the progression of the tumour in the bone marrow cavity, while the general condition of the animal remains satisfactory. While acute treatment with morphine has some analgesic effect on hind limb sparing the selective COX-2 inhibitor, celebrex, has no influence on the pain-related behavioural changes in this model.


Alcohol-Related Crimes And Risk Of Arrest For Intimate Partner Violence Among California Handgun Purchasers.
Intimate partner violence is a major public health problem in the US. Both firearms and alcohol have been documented to contribute to the risk and severity of this violence. Yet there has been little research examining the nexus of the two risk factors. This study sought to determine whether alcohol-related problems, as indicated by a history of conviction for offenses such as driving under the influence (DUI), were associated with risk for future intimate partner violence among authorized purchasers of handguns in California. Using a longitudinal cohort design, we found that purchasers with prior DUI convictions (and no other criminal history) had close to three times the risk of subsequent arrest for an intimate partner violence offense than did those with no criminal history at the time of the index firearm purchase. The regulation of firearm ownership among people with alcohol use problems may represent an important opportunity to reduce intimate partner violence and the escalation of firearm-related harm.


The air-ambulance: Orkney's experience.
The paramount problem for the delivery of the medical services in the Orkneys has been that of effective transport. The development of an efficient air-ambulance service has had a major impact on medical care. The service started in 1934, but was abolished at the outset of the Second World War and did not recommence until 1967. This paper examines the evolution of the air-ambulance service in the Orkney Islands, and describes alternative proposals for the use of aircraft in this region.


Educating the provider community about the new role of the peer review organization.
This report suggests an educational format that has been used successfully in Michigan to introduce the Health Care Quality Improvement Initiative to the medical community. The activities related to pattern analysis and the Fourth Scope of Work will require a collaborative effort between the medical community and the peer review organization (PRO). To improve understanding by providers and practitioners of pattern analysis, the Fourth Scope of Work, and the new PRO requirements, a series of educational programs was designed. The first presentation in the educational series included information about the changes between the Third and Fourth Scope of Work as well as the new structure within the PRO responsible for the pattern analysis activities: the Center for Health Outcomes and Evaluation. Descriptions of the process to be followed in interactions between the Center and providers and practitioners also were included: For the second session, a hands-on exercise was created to introduce the concept of a pattern. The exercise included graphic representations of patterns and a worksheet format to encourage the user to find specific data points within tables and graphs, describe a pattern in hospital outcome data, and verify that the same outcome pattern appeared in subgroups of hospitals and physicians. The third component in the educational series was a demonstration of the interaction between the Center and a hospital participating in a cooperative improvement project. Hospital-specific and physician-specific data, with appropriate comparative data, were provided to an audience made up of hospital administrators, practicing physicians, and allied health personnel who then worked through the issues related to data validation, definition of a project, agreement on interventions, and remeasurement of the outcome under study.


AlGaAs/GaAs/InGaAs pnp-type vertical-cavity surface-emitting transistor-lasers.
We report on the design, fabrication and analysis of vertical-cavity surface-emitting transistor-lasers (T-VCSELs) based on the homogeneous integration of an InGaAs/GaAs VCSEL and an AlGaAs/GaAs pnp-heterojunction bipolar transistor (HBT). Epitaxial regrowth confinement, modulation doping, intracavity contacting and non-conducting mirrors are used to ensure a low-loss structure, and a variety of design variations are investigated for a proper internal biasing and current injection to ensure a wide operating range. Optimized devices show mW-range output power, mA-range base threshold current and high-temperature operation to at least 60°C with the transistor in its active mode of operation for base currents well beyond threshold. Current confinement schemes based on pnp-blocking layers or a buried tunnel junction are investigated as well as asymmetric current injection for reduced extrinsic resistances.


Does the efficacy of dorsalis pedis artery bypasses vary among diabetic patients of different ethnic backgrounds?
Hispanic patients suffer from a high rate of leg amputations, far beyond what would be expected from the high prevalence of diabetes in this population. This raises questions about the efficacy of bypass operations across ethnic lines. We focused this review on dorsalis pedis bypasses, as these are frequently performed in diabetic patients. We compared outcomes between Hispanics and non-Hispanics and sought to identify factors predictive of failure or complications. The authors conducted a retrospective review of 144 dorsalis pedis bypasses in 106 men and 29 women with a mean age of 62 years. Eighty-two percent were Hispanic; 96% of cases were done for tissue loss, and 4% for rest pain. Twenty-five percent of patients experienced perioperative complications; these were more frequent in non-Hispanics than Hispanics (40% vs 22%, p = 0.05). The most frequent complications were wound related (11%). The 30-day mortality was 1.5% and 30-day graft thrombosis was 5%. Follow-up ranged from 1 to 62 months and averaged 12 months. Eighty-one percent of the limbs at risk were saved, although 36% of cases required minor foot amputations. Estimated primary graft patency was 68% at 30 months. The 30-month Kaplan-Meier curves for primary patency, assisted patency, and limb salvage were not statistically different between Hispanics and non-Hispanics (p > 0.4). Grafts that remained patent had higher duplex-derived intraoperative flow velocities in the dorsalis pedis artery than grafts that eventually failed (121 +/-69 vs 74 +/-26 cm/sec, p = 0.02). In grafts that remained patent, dorsalis pedis velocity decreased from the perioperative period to the 8 to 12 weeks time point, whereas no change was seen in grafts that eventually failed (mean decline of 48 +/-76 vs 1 +/-58 cm/sec, p = 0.02). No other factors were predictive of graft failure. The results of dorsalis pedis bypass in Hispanic patients compare favorably to those seen in other ethnic groups. This suggests that other factors must account for the high amputation rates seen in Hispanics, such as a frequent occurrence of nonreconstructible disease or unaccounted for cardiovascular risk factors. The usefulness of duplex-derived flow velocities in the dorsalis pedis to predict long-term graft patency warrants further investigation.


Changes in neurohormonal gut peptides following bariatric surgery.
The rising prevalence of obesity has reached pandemic proportions, with an associated cost estimated at up to 7% of health expenditures worldwide. Bariatric surgery is currently the only effective long-term treatment for obesity and obesity-related co-morbidities in clinically severely obese patients. However, the precise physiological mechanisms underlying the postsurgical reductions in caloric intake and body weight are poorly comprehended. It has been suggested that changes in hormones involved in hunger, food intake and satiety via the neurohormonal network may contribute to the efficacy of bariatric procedures. In this review, we consider how gastrointestinal hormone concentrations, involved in appetite and body weight regulation via the gut-brain axis, are altered by different bariatric procedures. Special emphasis is placed on neurohormonal changes following Roux-en-Y gastric bypass surgery, which is the most common and effective procedure used today.


Acute Subdural Hematoma in a High School Football Player After 2 Unreported Episodes of Head Trauma: A Case Report.
OBJECTIVE: To discuss the association between 2 unreported episodes of head trauma and an acute subdural hematoma in a high school football player; to address the role of the sport health care team in secondary schools when caring for an athlete with head trauma; and to recognize the importance of educating athletes and coaches about this condition. BACKGROUND: A previously healthy athlete experienced 2 unreported episodes of head trauma during a single game. The athlete was conscious and oriented to person, time, and place, but he vomited and complained of severe headache, nausea, and vertigo. During transfer, the athlete appeared to have a seizure. DIFFERENTIAL DIAGNOSIS: Subdural hematoma, epidural hematoma, intracerebral hemorrhage, second-impact syndrome, cervical spine injury, or epilepsy. TREATMENT: Computed tomography scan indicated fluid over the left frontal temporal fossa. Conservative treatment was begun, and the fluid resolved without incident. UNIQUENESS: A single episode of blunt trauma has been thought to cause an acute subdural hematoma. However, multiple concussions can also result in this condition. CONCLUSION: Single or multiple episodes of head trauma can lead to an acute subdural hematoma. This case study reflects the importance of proper education in the recognition and care of head trauma and return-to-play guidelines for athletes and coaches. A sport health care team in all secondary schools can provide the immediate and appropriate intervention for such injuries.


Efficacy of N-acetylcysteine in the treatment of nicotine dependence: a double-blind placebo-controlled pilot study.
Relapse is the rule rather than the exception in smokers aiming to quit smoking. Recently, evidence has emerged that glutamate transmission plays an important role in relapse. N-acetylcysteine (NAC), a cysteine prodrug, restores glutamate homeostasis and appears to be a potential new treatment for substance dependence. In the current pilot study, the effects of NAC on short-term abstinence of smoking were investigated. Subjects were heavy smokers randomized to receive placebo (n = 12) or NAC 3,600 mg/day (n = 10) in a double-blind fashion during 3.5 days. Subjects were asked to stop smoking and report on nicotine craving, nicotine withdrawal symptoms, and cigarette smoking during treatment. At the end of the treatment, subjects were invited to smoke a cigarette and to rate the rewarding effect of this cigarette. There was no significant effect of NAC on craving (p = 0.23, d = 0.52) and only a statistical trend towards fewer withdrawal symptoms in the NAC condition (p = 0.07, d = 0.80). Interestingly, subjects receiving NAC rated the first cigarette after the abstinence period of 3.5 days as significantly less rewarding than subjects on placebo (p = 0.04, d = 0.85). It is concluded that the results of this pilot study are encouraging and suggest that NAC might be a promising new treatment option for relapse prevention in nicotine dependence.


Decreased levels of active uPA and KLK8 assessed by [111 In]MICA-401 binding correlate with the seizure burden in an animal model of temporal lobe epilepsy.
Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [111 In]MICA-401. As the first step in exploring the applicability of [111 In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [111 In]MICA-401 distribution in the brain in two animal models: kainic acid-induced status epilepticus (KASE) and controlled cortical impact (CCI)-induced traumatic brain injury (TBI). In the KASE model, in vitro autoradiography with [111 In]MICA-401 was performed at 7 days and 12 weeks post-SE. To assess seizure burden, rats were monitored using video-electroencephalography (EEG) for 1 month before the 12-week time point. In the CCI model, in vitro autoradiography was performed at 4 days and ex vivo autoradiography at 7 days post-TBI. At 7 days post-SE, in vitro autoradiography revealed significantly decreased [111 In]MICA-401 binding in hippocampal CA3 subfield and extrahippocampal temporal lobe (ETL). In the chronic phase, when animals had developed spontaneous seizures, specific binding was decreased in CA3 and CA1/CA2 subfields of hippocampus, dentate gyrus, ETL, and parietal cortex. Of interest, KASE rats with the highest frequency of seizures had the lowest hippocampal [111 In]MICA-401 binding (r = -0.76, p ≤ 0.05). Similarly, at 4 days post-TBI, in vitro [111 In]MICA-401 binding was significantly decreased in medial and lateral perilesional cortex and ipsilateral dentate gyrus. Ex vivo autoradiography at 7 days post-TBI, however, revealed increased tracer uptake in perilesional cortex and hippocampus, which was likely related to tracer leakage due to blood-brain barrier (BBB) disruption. Strong association of reduced [111 In]MICA-401 binding with seizure burden in the KASE model suggests that analysis of reduced levels of active uPA/KLK8 represents a novel biomarker candidate to be explored as a biomarker for epilepsy severity. However, limited BBB permeability of [111 In]MICA-401 currently limits its application in vivo.


Early disruption of proximal anastomosis of a PTFE axillofemoral bypass graft.
Exertional disruption of axillary anastomosis is a well documented, although rare, complication of axillo-femoral grafts. Comprehension of causative mechanisms is of great importance, so that precautions can be taken against it. Here, a case of an early disruption of proximal anastomosis of an axillofemoral graft is reported. Use of crutches was incriminated as the responsible mechanism.


Fuel consumption and air emissions in one of the world's largest commercial fisheries.
The little information available on fuel consumption and emissions by high seas tuna fisheries indicates that the global tuna fleet may have consumed about 2.5 Mt of fuel in 2009, resulting in the production of about 9 Mt of CO2-equivalent greenhouse gases (GHGs), i.e., about 4.5-5% of the global fishing fleet emissions. We developed a model of annual fuel consumption for the large-scale purse seiners operating in the western Indian Ocean as a function of fishing effort, strategy, and vessel characteristics based on an original and unique data set of more than 4300 bunkering operations that spanned the period 2013-2019. We used the model to estimate the total fuel consumption and associated GHG and SO2 emissions of the Indian Ocean purse seine fishery between 1981 and 2019. Our results showed that the energetic performance of this fishery was characterized by strong interannual variability over the last four decades. This resulted from a combination of variations in tuna abundance but also changes in catchability and fishing strategy. In recent years, the increased targeting of schools associated with fish aggregating devices in response to market incentives combined with the IOTC management measure implemented to rebuild the stock of yellowfin tuna has strongly modified the productivity and spatio-temporal patterns of purse seine fishing. This had effects on fuel consumption and air pollutant emissions. Over the period 2015 to 2019, the purse seine fishery, including its support vessel component, annually consumed about 160,000 t of fuel and emitted 590,000 t of CO2-eq GHG. Furthermore, our results showed that air pollutant emissions can be significantly reduced when limits in fuel composition are imposed. In 2015, SO2 air pollution exceeded 1500 t, but successive implementation of sulphur limits in the Indian Ocean purse seine fishery in 2016 and 2018 have almost eliminated this pollution. Our findings highlight the need for a routine monitoring of fuel consumption with standardized methods to better assess the determinants of fuel consumption in fisheries and the air pollutants they emit in the atmosphere.


The CpG molecular structure controls the mineralization of calcium phosphate nanoparticles and their immunostimulation efficacy as vaccine adjuvants.
The co-precipitation of calcium phosphate nanoparticles (CaPs) in the presence of nucleotide chains such as polynucleotides (i.e., plasmid DNA and siRNA) and oligonucleotides has been extensively used for pre-clinical gene or drug delivery and immunotherapy studies. However, the exact role of these molecules in mineralization and tuning the physicochemical characteristics of the synthesized CaPs is still not entirely clear. In this study, we evaluated the effects of three different CpG oligodeoxynucleotides (ODN) and two representative nucleic acids (siRNA and DNA), when used as templates for the formation of CaPs. We examined the influence of CpGs with naturally-occurring phosphodiester or modified phosphorothioate backbones on the homogeneous formation of CaPs from a modified simulated body fluid solution. The hydrodynamic size, size polydispersity, morphology and surface charge of the CaPs were used as the most critical checkpoints to unravel the involved mechanisms. Our results show that the characteristics of CaPs are highly dependent on the composition, backbone, sequence and concentrations of the CpGs. The CpG type and concentration control the size distribution of the mineralized CaPs and their immunostimulation performance as verified by the activation of dendritic cells and secretion of the pro-inflammatory interleukin-6 (IL-6) cytokine, type I interferon-α (IFN-α) and co-stimulatory CD80, CD86 and CD40 markers. This study paves the way for better design of more efficient CaPs loaded with different types of CpGs for immunostimulation applications as vaccine adjuvants.


Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by protein kinase Cdelta.
Non-esterified fatty acid (free fatty acid)-induced activation of the novel PKC (protein kinase C) isoenzymes PKCdelta and PKCtheta correlates with insulin resistance, including decreased insulin-stimulated IRS-1 (insulin receptor substrate-1) tyrosine phosphorylation and phosphoinositide 3-kinase activation, although the mechanism(s) for this resistance is not known. In the present study, we have explored the possibility of a novel PKC, PKCdelta, to modulate directly the ability of the insulin receptor kinase to tyrosine-phosphorylate IRS-1. We have found that expression of either constitutively active PKCdelta or wild-type PKCdelta followed by phorbol ester activation both inhibit insulin-stimulated IRS-1 tyrosine phosphorylation in vivo. Activated PKCdelta was also found to inhibit the IRS-1 tyrosine phosphorylation in vitro by purified insulin receptor using recombinant full-length human IRS-1 and a partial IRS-1-glutathione S-transferase-fusion protein as substrates. This inhibition in vitro was not observed with a non-IRS-1 substrate, indicating that it was not the result of a general decrease in the intrinsic kinase activity of the receptor. Consistent with the hypothesis that PKCdelta acts directly on IRS-1, we show that IRS-1 can be phosphorylated by PKCdelta on at least 18 sites. The importance of three of the PKCdelta phosphorylation sites in IRS-1 was shown in vitro by a 75-80% decrease in the incorporation of phosphate into an IRS-1 triple mutant in which Ser-307, Ser-323 and Ser-574 were replaced by Ala. More importantly, the mutation of these three sites completely abrogated the inhibitory effect of PKCdelta on IRS-1 tyrosine phosphorylation in vitro. These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct phosphorylation of the IRS-1 molecule.


Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice.
Compound K (CK) is a major intestinal metabolite of ginsenosides derived from ginseng radix. In our preliminary studies, CK has shown to exhibit anti-hyperglycemic effect through its insulin-secreting action, similar to that of insulin secretagogue sulfonylureas. Metformin, a biguanide, improves insulin resistance by reducing gluconeogenesis and enhancing peripheral glucose uptake, promoting reduction of the plasma glucose level. The aim of this study was to compare the anti-diabetic effects of CK and metformin due to differences in their mechanisms of action and also to investigate whether treatment of CK and metformin in combination show synergistic or additive effects compared to each drug alone. Seven week-old male db/db mice were treated for 8 weeks. CK was given at a dose of 10 mg/kg, metformin at 150 mg/kg and the same dosage of each drug was applied to CK plus metformin combination group. Significant improvements were observed in plasma glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR) index and in hematoxylin and eosin-stained liver tissues in combination group. Although further studies to elucidate the benefits of co-administration of CK and metformin are needed, our findings may provide basis to the discovery of a new combination therapy on diabetes control in type 2 diabetics.


[Decrease in Mexico's life expectancy due to multiple homicides: the murder of women adjacent to the homicide of one or more men].
The objective is to analyze the effect of multiple homicides on male and female life expectancy and to provide empirical evidence of the temporal and spatial associations between male and female homicide rates by age group during the period 2002-2020. Using data from the National Institute of Statistics and Geography (INEGI) and population projections from the National Population Council (CONAPO), mortality rates due to homicide from 2002-2020 were estimated for both men and women, and the adjacency of homicides of men and women was analyzed, along with the spatial proximity between multiple homicides of men and women, along with changes in life expectancy due to homicide. Individual homicides have caused the greatest decrease in life expectancy for both men and women. The negative impact of multiple homicides on both female and male life expectancy began to draw attention in 2008. By analyzing the murders of women adjacent to the homicides of one or more men questions are raised about whether these crimes are primarily the result of criminal violence, and to a lesser extent the role of gender.


Hepatic resection of metastatic colorectal carcinoma: a ten-year experience.
Nineteen patients have undergone partial hepatectomy for metastatic colorectal carcinoma at UCLA during the past ten years, including five trisegmentectomies (TS), eight lobectomies (L), and six segmentectomies (SG), with only one (5.3%) mortality. Twelve lesions were solitary (S) and seven multiple (M). Mean survival is 27.4 months, with three patients surviving over five years and one nearly eight years. Better mean survival exists for S (33.2 months) compared with M (15.8 months) lesions; for lesser resections: SG (44.7 months), compared with L (24.3 months) and TS (11.0 months); and for those with delayed appearance of hepatic metastases: beyond two years (40.5 months), less than one year (24.8 months), and synchronous (23.1 months). Survival figures should improve, as none of the 12 surviving patients have evidence of recurrent disease and many have short follow-up. This experience defends aggressive surgical treatment of resectable colorectal carcinoma metastatic to liver, because systemic therapy is markedly less effective.


New method for study of peptide transport in bacteria.
The transport system for glycylmethionine in Escherichia coli B and Salmonella typhimurium LT2 was examined by a new approach which may be applied to other types of exogenous materials. Physiological auxotrophs were prepared by growing wild strains in a methionine-containing medium to repress the methionine biosynthetic enzymes. Immediate protein synthesis was shown to take place in such physiological auxotrophs only in the presence of either exogenous methionine or a methionine peptide, e.g., glycylmethionine. Protein synthesis was dependent on glycylmethionine taken up by the cell and was indicated by assaying for the inducible enzyme lysine decarboxylase at 5- to 15-min intervals. Uptake was studied by using low concentrations of glycylmethionine, therefore making uptake by permease the limiting step in incorporation of methionine into protein, and by addition of competitor peptides to media containing saturating concentrations of glycylmethionine. Lysine decarboxylase activity in S. typhimurium LT2 was about 80 times that present in E. coli B. Glycylmethionine transport had a K(m) of the order of 1 muM in S. typhimurium. Structural specificities observed for peptide transport by other workers were confirmed for E. coli B. Competitive inhibition of glycylmethionine uptake by dipeptides was observed in E. coli.


Some risk factors associated with Acid-alcohol-fast bacilli in patients with suspected pulmonary tuberculosis in jos, central Nigeria.
Mycobacterium tuberculosis remains a very serious public health problem due to its high tendency of person to person transmission, morbidity, and mortality. This study aimed at determining some risk factors associated with the prevalence of acid-alcohol-fast-bacilli (AAFB) within the study area. Sputum samples were collected from three hundred and three (303) patients with suspected cases of pulmonary tuberculosis in Jos. The samples were examined using Ziehl Neelson method. Structured questionnaires were administered to obtain some demographic data from patients that consented. Results were tested statistically for significance at p < 0.05 using Chi-square test. Out of the samples examined, 29 (9.60%), were positive for AAFB. The study showed that the prevalence of smear-positive increased with increase in number of persons sharing the same room. Statistically the study reveals that some risk factors such as alcoholism, cigarette smoking and number of persons staying in a household had a significant effects on the prevalence (p < 0.05),while HIV status had no significant effect on the prevalence (p > 0.05). There was high prevalence of AAFB in the study area especially among people living in poor/congested housing facilities and people with HIV/AIDS. This calls for more collaborative efforts and political will by government and non-governmental agencies in order to eradicate the infection rate within the area, and the country at large.


Conformations of two duplex forms of d(TCGA) in slow-exchange equilibrium characterized by NMR.
Two conformations adopted by the tetranucleoside triphosphate d(TCGA) in aqueous solution are in slow-exchange equilibrium on the NMR time scale. 1H and 31P NMR spectra obtained at temperatures below 25 degrees C contain two sets of signals that vary in relative proportions with changing temperature. High-field NMR techniques allow the conformations of these species to be examined. Both forms are right-handed double-helical structures, and their interconversion does not involve a single-stranded species since transfer of saturation is observed between corresponding imino protons held in the base pairs of each duplex. The form that predominates at higher temperatures resembles B-DNA, but the other, while of similar conformation at the ends of the molecule, is distorted at the C-G step. Shearing at the center of the duplex results in interstrand stacking of the two cytosines in a way that is reminiscent of Z-DNA. Distances between nonexchangeable protons in this model are consistent with nuclear Overhauser effects observed for resonances of the low-temperature form, while the 1H NMR spectrum shows cytidine H-2' resonances at unusually high field. The relative stabilities of the two forms are discussed in terms of base stacking and hydration, but the origin of the high activation energy for interconversion implicit in the slow-exchange rate is unclear. The conformation of the low-temperature form may represent a sequence-dependent structural feature important in natural DNA, although somewhat fortuitously exemplified by this tetramer. The suggested involvement in correct nucleosome phasing of the pentamer d(TTCGA), present in some eukaryotic genes, is noted.


Topoisomerase mutations in fluoroquinolone-resistant and methicillin-susceptible and -resistant clinical isolates of Staphylococcus aureus.
The incidence of the various mutations in the genes encoding topoisomerase IV and DNA gyrase in fluoroquinolone-resistant clinical isolates of Staphylococcus aureus is not known. Using restriction fragment length polymorphism analysis and DNA sequencing, we found that in fluoroquinolone- and methicillin-resistant strains, mutations in grlA and gyrA are quite likely to be present together. For fluoroquinolone-resistant but methicillin-susceptible strains, mutations in grlA alone are more common.


Use of in vitro reconstructed skin To cover skin flap donor site.
The skin flap technique is widely used in reconstructive surgery for the coverage of deep burns of the face, neck, and joints. Facial deformities and joint contractures are avoided by transplanting vascularized full-thickness skin on wounds. The major drawback of this technique is the injury inflicted upon the donor site, which corresponds to a third degree burn. The usual technique to cover the flap donor site is the transplantation of split-thickness autografts. In the case of patients with deep and extensive burns, the harvesting of good quality autografts is often difficult because of multiple scars. In order to avoid additional trauma to the patient by split-thickness skin harvesting, we have experimented the use of a new model of in vitro reconstructed skin graft for flap donor site coverage in a mouse model. The reconstructed skin was grafted on the back of nude mice at the skin flap donor site, while flap was used to cover a wound generated on joint of the posterior leg. A 100% graft take was achieved (16 mice were used) and a limited contraction of the reconstructed skin was observed 30 days posttransplantation (78% of the initial surface area of the graft remained). Histological analysis of the graft demonstrated healing of a well differentiated epidermis laying on a dense dermis. Since this technique would prevent additional trauma to the patient while achieving a good healing of the wound, it may be a useful approach in the coverage of skin flap donor site in humans.


Expression and chromosomal localization of the cytochrome P1-450 gene in human mitogen-stimulated lymphocytes.
Genetic differences in aryl hydrocarbon hydroxylase (AHH) (flavoprotein-linked monoxygenase EC 188.8.131.52) activity in cultured lymphocytes have been linked with individual risk for certain environmentally caused cancers. Cytochrome P1-450 is the form of cytochrome P-450 most closely associated with AHH activity. In this study the chromosomal localization and the expression of human cytochrome P1-450 gene were determined in phytohemagglutinin-stimulated lymphocytes. In situ hybridization analysis provides assignment of the structural gene for human cytochrome P1-450 to chromosome 15q22-q24. Treatment of lymphocytes with benzanthracene increased the amount of mRNA hybridized to the cloned cytochrome P1-450 gene. The level of cytochrome P1-450 mRNA in these lymphocytes correlates well with the induced AHH activity indicating that non-cytochrome P1-450 enzymes contribute little to the individual differences in the level of AHH activity in the lymphocytes. Southern analyses of genomic DNA from individuals with high and low induced AHH activity demonstrated no detectable differences in the pattern or intensity of restriction fragments after treatment with benzanthracene from either individual. This finding together with the excellent correlation between the induced cytochrome P1-450 and AHH activity, suggests that transcriptional control rather than gene amplification or gross form of gene rearrangement accounts for cytochrome P1-450 induction in man. Measurements of cytochrome P1-450 mRNA content in cultured lymphocytes provide an alternative approach to the assay of AHH activity in assessing AHH phenotype and predicting different susceptibilities to deleterious environmental agents.


A change in the geodynamics of continental growth 3 billion years ago.
Models for the growth of continental crust rely on knowing the balance between the generation of new crust and the reworking of old crust throughout Earth's history. The oxygen isotopic composition of zircons, for which uranium-lead and hafnium isotopic data provide age constraints, is a key archive of crustal reworking. We identified systematic variations in hafnium and oxygen isotopes in zircons of different ages that reveal the relative proportions of reworked crust and of new crust through time. Growth of continental crust appears to have been a continuous process, albeit at variable rates. A marked decrease in the rate of crustal growth at ~3 billion years ago may be linked to the onset of subduction-driven plate tectonics.


[THE STATUS OF THE SERVICE OF MEDICAL STATISTICS ACCORDING TO THE STAFF SURVEY RESULTS].
The Medical Statistics Service plays an important role in providing a medical organization with timely, high-quality statistical information. Therefore, it is important to study the opinions of specialists on the organization of this work. To analyze the opinions of the staff of departments (offices) of medical statistics on the current work organization. A survey was conducted among employees of the departments (offices) of medical statistics of the Moscow inpatient facilities. The survey results are presented as a frequency (in percent) of the choice of the answer options with a 95% confidence interval. Frequency confidence intervals were calculated using the EpiInfo 7 program. A total of 103 employees of the departments of medical statistics of the Moscow inpatient facilities took part in the survey. The majority of the respondents has a 20-year experience or more (29.1%). 61.3% of the heads of the departments of medical statistics, 70.4% of the doctors-statisticians and 74.2% of the medical statisticians stated a lack of a qualification category. The majority of the respondents were positive in their evaluation of the work organization of the medical statistics service (79.6%). The significance (importance) of the medical statistics service is unconditionally understood by 86.4% of the respondents. The respondents demonstrated a high degree of job satisfaction and work environment (10 scores out of 10). The study has identified a fairly positive attitude of the respondents towards their work, and the medical statistics service in general. However, the results obtained have also raised new questions, in particular, why specialists in this area do not have qualification categories, why they are not satisfied with the possibility of career growth, etc.


The Quality of Life in Chronic Patients in the Process of Rehabilitation.
The aim of this study was to examine whether there is a correlation between self-evaluated quality of life, anxiety, depression, motivation, subjective-rated financial status, education, age and autonomous movements in patients with chronic conditions. The study consecutively included 68 chronically ill patients, the average chronological age of 56.21 years. The Hospital Anxiety and Depression Scale for self-evaluation of the quality of life of respondents was used to evaluate the presence of anxiety and depression, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form was used for self-evaluation of the quality of life, and the Visual analogue scale of motivation was used for self-evaluation of the level of motivation. It was found that anxiety, depression, education, financial status, chronological age and mobility have a significant impact on the sense of satisfaction with the quality of life of patients with chronic diseases. These results are important for clinical practice, planning and delivery of health services, evaluation of the implemented public health measures.


Chromatin dynamics during differentiation of myeloid cells.
Cellular commitment to differentiation requires a tightly synchronized, spatial-temporal interaction of regulatory proteins with the basic DNA and chromatin. A complex network of mechanisms involving induction of lineage instructive transcription factors, installation or removal of histone modifications and changes in the DNA methylation pattern locally orchestrate the three-dimensional chromatin structure and determine cell fate. Maturation of myeloid lineages from hematopoietic stem cells has emerged as a powerful model to study those principles of chromatin mechanisms in cellular differentiation and lineage fate selection. This review summarizes recent knowledge and puts forward novel ideas on how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation and leukemic transformation outcome.


Imaging of acute stroke.
The utility of diagnostic imaging during the critical first few hours after stroke onset has many important applications. First and foremost, imaging technologies that can reliably detect and quantify the location of acute stroke will greatly enhance the clinician's ability to accurately diagnose individual stroke patients. Secondly, if imaging technology could provide information about the likely severity of the ischemic injury, patient prognosis and management would be enhanced. The possibility of potentially distinguishing severely injured and likely irreversible ischemic brain tissue from ischemic tissue likely not yet irreversibly injured may soon be attainable. The ability of imaging technology to reliably distinguish the status of focally ischemic brain will presumably dramatically impact upon patient management. This information, along with the data about the severity and extent of blood flow and tissue perfusion abnormalities, will help acute stroke care evolve beyond rigid time windows to individualized, pathophysiologically based treatment decisions. Not only will decisions to treat or not be made based upon imaging-derived status, but also the most appropriate type of therapy to be employed, i.e. thrombolysis, neuroprotection, therapy to reduce secondary reperfusion-related injury or combinations of these modalities. In this brief and necessarily incomplete overview of acute stroke imaging, the focus will be on new developments in CT and MRI.


Janthinobacterium CG23_2: Comparative Genome Analysis Reveals Enhanced Environmental Sensing and Transcriptional Regulation for Adaptation to Life in an Antarctic Supraglacial Stream.
As many bacteria detected in Antarctic environments are neither true psychrophiles nor endemic species, their proliferation in spite of environmental extremes gives rise to genome adaptations. Janthinobacterium sp. CG23_2 is a bacterial isolate from the Cotton Glacier stream, Antarctica. To understand how Janthinobacterium sp. CG23_2 has adapted to its environment, we investigated its genomic traits in comparison to genomes of 35 published Janthinobacterium species. While we hypothesized that genome shrinkage and specialization to narrow ecological niches would be energetically favorable for dwelling in an ephemeral Antarctic stream, the genome of Janthinobacterium sp. CG23_2 was on average 1.7 ± 0.6 Mb larger and predicted 1411 ± 499 more coding sequences compared to the other Janthinobacterium spp. Putatively identified horizontal gene transfer events contributed 0.92 Mb to the genome size expansion of Janthinobacterium sp. CG23_2. Genes with high copy numbers in the species-specific accessory genome of Janthinobacterium sp. CG23_2 were associated with environmental sensing, locomotion, response and transcriptional regulation, stress response, and mobile elements-functional categories which also showed molecular adaptation to cold. Our data suggest that genome plasticity and the abundant complementary genes for sensing and responding to the extracellular environment supported the adaptation of Janthinobacterium sp. CG23_2 to this extreme environment.


Frightening visual hallucinations: atypical presentation of Charles Bonnet syndrome triggered by the Black Saturday bushfires.
Charles Bonnet syndrome (CBS) is a disorder in which psychologically normal people, often with vision impairment, experience complex visual hallucinations. The hallucinations are purely visual and do not occur in any other sensory modality, and people with CBS have full insight into the unreal nature of the hallucinations. This report describes the case of a CBS sufferer who experienced a distressing change in the nature of her visual hallucinations following a stressful event--the Black Saturday bushfires of February 2009.


Nurses' Knowledge and Treatment Beliefs: Use of Complementary and Alternative Medicine for Pain Management.
Purpose: To examine the relationship between nurses' knowledge, attitudes, and beliefs about medicines, in general, and complementary and alternative medicine (CAM) and identify the predictors of referrals for pain management. Method: This descriptive, correlational study utilized an online survey to collect data from direct care nurses at a large medical center in southeastern United States. The online survey consisted of the Complementary and Alternative Medicines and Beliefs Inventory (CAMBI), the Beliefs about Medicine Questionnaire, and four open-ended questions. Referral data were obtained from the Information Management Department at this medical center. Results: Among the 218 nurses who completed the survey (15.12%), majority (85%) supported CAM use, but only 32% reported utilizing CAM therapies with patients. Medical surgical, emergency department, and perioperative nurses scored higher on their CAMBI total score and were more likely to refer for CAM therapies when compared with intensive care unit nurses. Conclusions: Beliefs about CAM specifically were not related to referrals for CAM therapies. This study suggests the need for further education on the nurse's role in CAM usage. Understanding the link between nurses' knowledge, attitudes, and treatment beliefs and their relationship to CAM usage provides direction for future educational interventions.


Efficacy of the radial acquisition regime (RADAR) for acquiring head and neck MR images.
To investigate the efficacy of the radial acquisition regime (RADAR) for acquiring head and neck MR images. 15 healthy volunteers underwent imaging with 4 sequences [fast spin echo T2 weighted imaging (FSE-T2WI), RADAR T2 weighted imaging (RADAR-T2WI), single-shot echo planar imaging diffusion-weighted imaging (SS-EPI-DWI) and RADAR diffusion-weighted imaging (RADAR-DWI)]. Both standard images and images during periodic mouth motion were acquired. Two radiologists scored the overall image artefacts and detectability of several anatomical structures without knowledge of sequence type. For each sequence, image distortion was quantitatively compared by the anteroposterior to right-left ratio of several anatomical structures. The mean scores of artefacts and distortion of several anatomical structures were compared using the multiple comparison test. The detectabilities were compared using the Wilcoxon signed-rank test. Regardless of mouth motion, RADAR-T2WI was significantly superior to FSE-T2WI in artefacts and oral-area detectability (p < 0.01), and RADAR-DWI was significantly superior to SS-EPI-DWI in terms of artefacts (p < 0.01). In terms of image distortion, RADAR-DWI was significantly superior to SS-EPI-DWI (p < 0.01). RADAR-T2WI could replace FSE-T2WI as a conventional T2WI protocol for the head and neck. For the RADAR-DWI sequence, validation studies are needed. Advances in knowledge: RADAR-T2WI was superior to FSE-T2WI with regard to artefacts and detectability, and RADAR-DWI was superior in terms of artefacts compared with SS-EPI-DWI.


Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice.
Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV.


General transfer-matrix method for optical multilayer systems with coherent, partially coherent, and incoherent interference.
The optical response of coherent thin-film multilayers is often represented with Fresnel coefficients in a 2 x 2 matrix configuration. Here the usual transfer matrix was modified to a generic form, with the ability to use the absolute squares of the Fresnel coefficients, so as to include incoherent (thick layers) and partially coherent (rough surface or interfaces) reflection and transmission. The method is integrated by use of models for refractive-index depth profiling. The utility of the method is illustrated with various multilayer structures formed by ion implantation into Si, including buried insulating and conducting layers, and multilayers with a thick incoherent layer in an arbitrary position.


Understanding Sources of Knowledge for Coaches of Athletes with Intellectual Disabilities.
Recent research has investigated development of coaching knowledge; however, less research has investigated the development of coaches who coach athletes with intellectual disabilities. The purpose of this study was to understand how coaches of athletes with intellectual disabilities gain their knowledge. Forty-five Special Olympics Canada coaches participated in structured telephone interviews investigating actual and ideal sources of coaching knowledge. Coaching knowledge was categorized across the dimensions of competition, organization and training. Coaches primarily learned by doing and by consulting with coaching peers. Information about ideal sources of coaching knowledge demonstrates that coaches would value structured coaching courses, learning from mentors and from administrative support, in addition to learning on their own and from peers. Results suggest that a broader approach to education should be incorporated into coaching athletes with intellectual disabilities. Recommendations for achieving such goals are provided.


Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.
Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED.


Epithelial interactions and local engraftment of lung-resident mesenchymal stem cells.
Multipotent mesenchymal progenitor cells, termed "mesenchymal stem cells" (MSCs), have been demonstrated to reside in human adult lungs. However, there is little information regarding the associations of these local mesenchymal progenitors with other resident somatic cells and their potential for therapeutic use. Here we provide in vivo and in vitro evidence for the ability of human adult lung-resident MSCs (LR-MSCs) to interact with the local epithelial cells. The in vivo retention and localization of human LR-MSCs in an alveolar microenvironment was investigated by placing PKH-26 or DsRed lentivirus-labeled human LR-MSCs in the lungs of immunodeficient (SCID) mice. At 3 weeks after intratracheal administration, 19.3 ± 3.21% of LR-MSCs were recovered, compared with 3.47 ± 0.51% of control fibroblasts, as determined by flow cytometry. LR-MSCs were found to persist in murine lungs for up to 6 months and demonstrated preferential localization to the corners of the alveoli in close proximity to type II alveolar epithelial cells, the progenitor cells of the alveolar epithelium. In vitro, LR-MSCs established gap junction communications with lung alveolar and bronchial epithelial cells and demonstrated an ability to secrete keratinocyte growth factor, an important modulator of epithelial cell proliferation and differentiation. Gap junction communications were also demonstrable between LR-MSCs and resident murine cells in vivo. This study demonstrates, for the first time, an ability of tissue-specific MSCs to engraft in their organ of origin and establishes a pathway of bidirectional interaction between these mesenchymal progenitors and adult somatic epithelial cells in the lung.


Electrospray ionization mass spectrometric analysis of microcystins, cyclic heptapeptide hepatotoxins: modulation of charge states and [M + H]+ to [M + Na]+ ratio.
Electrospray ionization mass spectrometry was used to develop a rapid, sensitive, and accurate method for determination and identification of hepatotoxic microcystins, cyanobacterial cyclic heptapeptides. To optimize the electrospray ionization conditions, factors affecting charge state distribution, such as amino acid components of sample, proton affinity of the additives, and additive concentration, were investigated in detail and a method for controlling charge states was developed to provide molecular-related ions for assignment of molecular weight and reasonably abundant precursor ions for MS/MS analysis. A procedure for identification of microcystins consisting of known amino acids was proposed: for microcystins giving abundant [M + 2H]2+ ions, the addition of nitrogen-containing bases to the aqueous sample solution is effective to obtain an increased intensity of [M + H]+ ions, whereas the addition of Lewis acids containing nitrogen can produce increased abundances of [M + 2H]2+ ions for microcystins giving weak [M + 2H]2+ ions. Microcystins possessing no arginine residue always give sodium adduct ions [M + Na]+ as the base peak, and these are difficult to fragment via low energy collision-induced dissociation to yield structurally informative products; the addition of oxalic acid increases [M + H]+ ion abundances, and these fragment readily.


Citizens' use of digital media to connect with health care: Socio-ethical and regulatory implications.
Digital technologies promise to transform practices of health, medicine and health care and 'power' economies. In expectation of their presumed future benefits, governments in recent years have invested heavily in new technology initiatives and have sought to engender 'digital literacy' among citizens. This article introduces papers and expands on themes arising from a special issue that explores the socio-ethical and regulatory implications of citizens' use of digital media to connect with health care. We set the scene by examining the promissory discourse that attaches to digital technologies as applied to health care, and its role in shaping actions, and then consider the longer term prospects and implications of digitalisation for conceptions of citizenship and established categories and distinctions. As we argue, given the history of new technologies, the longer term implications of digitalisation are likely to differ significantly from those envisaged. Digital technologies promise radical positive disruption. Yet many uncertainties accompany their development and future applications and likely implications. Making reference to papers in the special issue and the wider literature, the article considers the prospects of digitalisation in medicine and health care in light of the colonisation of the Internet by powerful technology companies, the shift in capitalist economies from processes of production to technologies of prediction, evidence of inequalities in access to the Internet and related devices, and the growing number of data breaches involving personal health information. We draw attention to the failure of governments to engage citizens in substantive deliberations about digitalisation and its future potential implications and the ultimate democratic deficit that this represents. We ask, what does it mean to 'regulate' digital media in a context in which data are widely viewed as the 'new oil'? While we have no straightforward answers, we suggest that recent legislative efforts (e.g. General Data Protection Regulation in Europe) and growing calls for 'algorithmic accountability' have the potential to temper the more harmful aspects of digitalisation.


Novel melt-processable chitosan-polybutylene succinate fibre scaffolds for cartilage tissue engineering.
Novel chitosan/polybutylene succinate fibre-based scaffolds (C-PBS) were seeded with bovine articular chondrocytes in order to assess their suitability for cartilage tissue engineering. Chondrocytes were seeded onto C-PBS scaffolds using spinner flasks under dynamic conditions, and cultured under orbital rotation for a total of 6 weeks. Non-woven polyglycolic acid (PGA) felts were used as reference materials. Tissue-engineered constructs were characterized by scanning electron microscopy (SEM), hematoxylin-eosin (H&E), toluidine blue and alcian blue staining, immunolocalization of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification at different time points. SEM showed the chondrocytes' typical morphology, with colonization at the surface and within the pores of the C-PBS scaffolds. These observations were supported by routine histology. Toluidine blue and alcian blue stains, as well as immunohistochemistry for collagen types I and II, provided qualitative information on the composition of the engineered extracellular matrix. More pronounced staining was observed for collagen type II than collagen type I. Similar results were observed with constructs engineered on PGA scaffolds. These also exhibited higher amounts of matrix glycosaminoglycans and presented a central region which contained fewer cells and little matrix, a feature that was not detected with C-PBS constructs.


Lung volume, diffusing capacity, chest roentgenogram and dyspnea index in interstitial lung disease.
To investigate the physiologic impairment and the role played by pulmonary function tests in interstitial lung disease (ILD), we performed spirometry tests and tested the single-breath carbon monoxide diffusing capacity of 27 patients with diffuse interstitial pulmonary fibrosis (DIPF) and 35 patients with collagen vascular disease (CVD). All of the patients showed irregular linear opacities on their chest X-ray films. Corresponding chest roentgenograms for each patient were evaluated according to the International Labour Organization (ILO) classification. A modified Baseline Dyspnea Index (BDI), which incorporate a patient's physical activity into the recording, was used to quantitate dyspnea. Patients with DIPF demonstrated a comparable reduction in both lung volumes and diffusing capacity. In contrast, patients with CVD had a greater reduction in diffusing capacity than in forced vital capacity (FVC) and total lung capacity (TLC). There were no significant correlations between the type of linear opacities and the severity of the pulmonary function abnormalities, or between the opacities and the dyspnea in either disease group. The profusion of pulmonary infiltrates also did not affect the lung function except for diffusing capacity in patients with DIPF. However, there was a significant loss of FVC, TLC, forced expiratory volume in one second (FEV1) and diffusing capacity with increasing levels of dyspnea. We conclude that pulmonary function parameters may not be equally affected in DIPF and CVD. Approaches using the ILO classification for analysis of chest roentgenograms provide limited information regarding the functional status of patients. Pulmonary functions are significantly related to the extent of a patient's physical activity, if the severity of dyspnea is evaluated carefully using a quantifiable system.


Results of routine preoperative coronary angiography in tetralogy of Fallot.
In the surgical repair of tetralogy of Fallot, morvidity and mortality are increased by certain coronary anomalies, in particular, an anterior descending branch originating from the right coronary artery or a single coronary artery in which a large coronary branch runs across the pulmonary outflow tract. In series of 94 patients with tetralogy of Fallot who underwent cardiac catheterization, coronary artery visualization was attempted routinely, most often by flush aortography using a venous catheter. Diagnostic coronary visualization was obtained in 84 patients (89%). In these, the incidence of recognized coronary anomalies was 5%; anterior decending from the right coronary artery in four patients (4%), and singly left coronary in one patient (1%). In 195 autopsied cases of tetralogy, the incidence of coronary anomalies was also 5%. Routine preoperative demonstration of the coronary artery anatomy in tetralogy patients usually can be accomplished satisfactorily and conveniently by transvenous flush aortography.


[Listeria monocytogenes: a dangerous pathogen used as a vector for the new generation of vaccines].
Listeria monocytogenes (LM) has become a major pathogen of human foodborne illnesses eliciting meningitis, peritonitis, and abortions with a mortality rate of about 30%. During the course of the disease, LM infects a variety of tissues and cell types due to its capacity to induce its own phagocytosis even into non-phagocytic cells. For over 35 years LM continues to serve as a model to define general paradigms of immunology In this review we focus on the clinical characteristics of listeriosis, on the risk factors involved in the pathogenesis, and discuss the currently accepted approaches to prophylaxis and treatment. We report on novel strategies in vaccine development based on the LM-dependent delivering machinery for immune recognition and induction of immunological memory against desired antigens.


Oxidative protein damage in type I diabetic patients with and without complications.
To examine the influence of oxidative stress on oxidative protein damage, we studied 47 Type I diabetic patients with and without complications. We determined plasma protein carbonyl, plasma protein thiol and nitrotyrosine levels as markers of oxidative protein damage, plasma lipid hydroperoxide levels as markers of oxidative stress, and plasma total thiol, plasma nonprotein thiol, erythrocyte glutathione, plasma ceruloplasmin, transferrin and total iron binding capacity as markers of free radical scavenging. There were no significant differences in nitrotyrosine, total plasma thiol, protein thiol, and erythrocyte glutathione levels between diabetic patients with complications and without complications. However, plasma protein carbonyl, lipid hydroperoxide, and nonprotein thiol levels were significantly increased in diabetic patients with complications compared with diabetic patients without complications. Although redox status of plasma is impaired in diabetic patients, we suppose these significantly different markers reflect enhanced oxidative protein damage in diabetic patients with complications.


Responses of juxtaglomerular cell suspensions to various stimuli.
Cell suspensions were prepared from rat renal cortical tissue by dispersion with 0.1% collagenase. Unit gravity sedimentation in a 1%-4% Ficoll gradient resulted in a single-cell suspension enriched in juxtaglomerular (JG) cells. Both the cellular renin activity and the amount of renin released into the supernatant increased with time when the suspensions were incubated for 1 hour at 37 degrees C in tissue culture medium. These cells responded to epinephrine and norepinephrine by increasing both synthesis and release of renin. The response was blocked by timolol but not by phenoxybenzamine. Cell suspensions prepared in the same manner but using 0.25% trypsin as the dispersing enzyme neither synthesized nor released renin into the tissue culture medium when similarly incubated. Trypsin-dispersed cells did not respond to catecholamine stimulation. Renin synthesis and release in collagenase-dispersed JG cells were unaltered by changes in Na, K, or Ca ion concentrations. Angiotensin II inhibited release, while saline extracts of clipped kidney from renal hypertensive rats stimulated renin release by these cells.


A randomized controlled trial of telemonitoring in older adults with multiple chronic conditions: the Tele-ERA study.
Older adults with multiple chronic illnesses are at risk for worsening functional and medical status and hospitalization. Home telemonitoring may help slow this decline. This protocol of a randomized controlled trial was designed to help determine the impact of home telemonitoring on hospitalization. The specific aim of the study reads as follows: to determine the effectiveness of home telemonitoring compared with usual care in reducing the combined outcomes of hospitalization and emergency department visits in an at-risk population 60 years of age or older. Two-hundred patients with the highest 10% Mayo Clinic Elder Risk Assessment scores will be randomly assigned to one of two interventions. Home telemonitoring involves the use of a computer device, the Intel Health Guide, which records biometric and symptom data from patients in their homes. This information is monitored by midlevel providers associated with a primary care medical practice. Under the usual care scenario, patients make appointments with their providers as problems arise and use ongoing support such as a 24-hour nurse line.Patients will have initial evaluations of gait and quality of life using instruments such as the SF-12 Health Survey, the Kokmen Short Test of Mental Status, and the PHQ-9 health questionnaire. Patients will be followed for 1 year for primary outcomes of hospitalizations and emergency department visits. Secondary analysis will include quality of life, compliance with the device, and attitudes about telemonitoring. Sample size is based on an 80% power to detect a 36% difference between the two groups. The primary analysis will involve Cox proportional time-to-event analysis. Secondary analysis will use t-test comparisons for continuous variables and the chi square test for proportional analysis. Patients randomized to home telemonitoring will have daily assessments of their health status using the device. Registered nurse monitoring will assess any change in status followed by videoconferencing by a mid-level provider. We obtained trial registration and Institutional Review Board approval. Trial registration number through http://www.clinicaltrials.gov: NCT01056640.


Rapid increase in dispersal during range expansion in the invasive ladybird Harmonia axyridis.
The evolutionary trajectories associated with demographic, genetic and spatial disequilibrium have become an issue of growing interest in population biology. Invasive species provide unique opportunities to explore the impact of recent range expansion on life-history traits, making it possible to test for a spatial arrangement of dispersal abilities along the expanding range, in particular. We carried out controlled experiments in laboratory conditions to test the hypothesis of an increase in dispersal capacity with range expansion in Harmonia axyridis, a ladybird that has been invading Europe since 2001. We found a marked increase in the flight speed of the insects from the core to the front of the invasion range in two independent sampling transects. By contrast, we found that two other traits associated with dispersal (endurance and motivation to fly off) did not follow the same spatial gradient. Our results provide a striking illustration of the way in which predictable directional genetic changes may occur rapidly for some traits associated with dispersal during biological invasions. We discuss the consequences of our results for invasion dynamics and the evolutionary outcomes of spatially expanding populations.


Safe transport of critically ill adult patients on extracorporeal membrane oxygenation support to a regional extracorporeal membrane oxygenation center.
Patients with severe cardiac or pulmonary failure who require transport to specialized hospitals currently pose a challenge. Mechanical support in the form of extracorporeal membrane oxygenation (ECMO) may increase the safety of transporting such patients to an institution where they will have access to advanced medical therapy. Over 2.5 years, 17 patients were successfully cannulated and placed on a simplified ECMO circuit at other institutions and transported via ambulance to our hospital. Fourteen patients with acute respiratory distress syndrome (ARDS) were placed on venovenous (VV) ECMO. Two patients with isolated cardiogenic shock and one patient with ARDS were placed on venoarterial (VA) ECMO. The two cardiogenic shock patients were converted to a biventricular assist device shortly after arrival. The median unit-to-unit transport time was 60 minutes (interquartile range 50-92 minutes), and the median distance traveled was 23 miles (interquartile range 17-55 miles). There was no transport-related morbidity or mortality. The median duration of ECMO support was 8 days (interquartile range 4-11 days). Thirteen patients (76%) were successfully decannulated. Ten patients (59%) were weaned from the ventilator, and nine patients (53%) survived up to 3 months and were discharged from the hospital. Critically ill patients with severe ARDS or cardiogenic shock can be safely transported on VV or VA ECMO support to regional ECMO centers. As the indications and demands for ECMO support expand, so will the role for transporting patients on ECMO.


Traumatic longitudinal atlanto-occipital distraction injuries in children.
Traumatic atlanto-occipital dislocation with survival is possible and, in fact may be relatively more common than once thought. The spectrum of neurologic manifestations is broader than previously described and does not necessarily end in death or tragic neurologic deficit. Radiographic diagnosis of this injury may be difficult, particularly in the longitudinal distraction-dislocation type. Although several methods have been proposed to evaluate the atlanto-occipital relationship, none of these is infallible in the recognition of distraction injury in children. Immobilization rather than skeletal traction provides sufficient immediate stabilization when the dislocation at the atlanto-occipital junction is of the longitudinal distraction type. Three cases are reported: in one, death occurred early; in the second, recovery was partial, but sudden death occurred 2 years later; the third child recovered fully.


Save the last dance for me: unwanted serial position effects in jury evaluations.
Whenever competing options are considered in sequence, their evaluations may be affected by order of appearance. Such serial position effects would threaten the fairness of competitions using jury evaluations. Randomization cannot reduce potential order effects, but it does give candidates an equal chance of being assigned to preferred serial positions. Whether, or what, serial position effects emerge may depend on the cognitive demands of the judgment task. In end-of-sequence procedures, final scores are not given until all candidates have performed, possibly burdening judges' memory. If judges' evaluations are based on how well they remember performances, serial position effects may resemble those found with free recall. Candidates may also be evaluated step-by-step, immediately after each performance. This procedure should not burden memory, though it may produce different serial position effects. Yet, this paper reports similar serial position effects with end-of-sequence and step-by-step procedures used for the Eurovision Song Contest: Ratings increased with serial position. The linear order effect was replicated in the step-by-step judgments of World and European Figure Skating Contests. It is proposed that, independent of the evaluation procedure, judges' initial impressions of sequentially appearing candidates may be formed step-by-step, yielding serial position effects.


Companion animals in palliative care: stories from the bedside.
Research has shown that a companion animal or pet can help a person better cope with stressful life events, prevent loneliness, decrease depression, improve activities of daily living (ADLs), and increase social interactions. Pets in nursing homes have been associated with decreased psychotropic medication usage and a greater than 50 percent reduction in healthcare costs. Despite research in other areas of healthcare, there is limited data concerning the use of companion animals in palliative care. This article presents an overview of companion-animal-associated medical research as well as patient stories that illustrate the roles of companion animals in end-of-life care.


Tumor suppressor FOXO3 regulates ribonucleotide reductase subunit RRM2B and impacts on survival of cancer patients.
The role of Ribonucleotide reductase (RR) subunits in different cancers has been intensively studied in our laboratory. RRM2B was identified as a p53-inducible RR subunit that involves in various critical cellular mechanisms such as cell cycle regulation, DNA repair and replication, and mitochondrial homeostasis, etc. However, little is known about the p53-independent regulation of RRM2B in cancer pathology. In this study, we discovered tumor suppressor FOXO3 as the novel regulator of RRM2B. FOXO3 directly bound to and transcriptionally activated the promoter of RRM2B, and induced the expression of RRM2B at RNA and protein levels. Moreover, Overexpression of RRM2B and/or FOXO3 inhibited the proliferation of cancer cells. The cancer tissue microarray data also demonstrated a strong correlation between the co-expression of FOXO3 plus RRM2B and increased disease survival and reduced recurrence or metastasis in lung cancer patients. Our results suggest a novel regulatory control of RRM2B function, and imply the importance of FOXO signaling pathway in DNA replication modulation. This study provides the first time evidence that RRM2B is transcriptionally and functionally regulated independent of p53 pathway by FOXO3, and it establishes that FOXO3 and RRM2B could be used as predictive biomarkers for cancer progression.


Identification of the poly(C) binding protein in the complex associated with the 3' untranslated region of erythropoietin messenger RNA.
Hypoxia regulates expression of erythropoietin (EPO), a glycoprotein that stimulates erythrocytosis, at the level of transcription and also possibly at the level of messenger RNA (mRNA) stability. A pyrimidine-rich region within the EPO mRNA 3' untranslated region was implicated in regulation of EPO mRNA stability element and shown to bind protein factors. In the present study we wished to identify the protein factor binding to the pyrimidine-rich sequence in the EPO mRNA stability element. Using mobility shift assays, ultraviolet light cross-linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and electroelution of protein factors from the gel slices corresponding to the ribonucleoprotein complexes, we found that two isoforms of a 40 kD poly(C) binding protein (PCBP, also known as alphaCP or hnRNPE), PCBP1, and PCBP2 are present in that complex. In Hep3B or HepG2 cells hypoxia induces neither expression of PCBP nor formation of the ribonucleoprotein complex associated with EPO mRNA that involves PCBP.


The challenge of comparative health policy for political science.
After a brief review of the literature and some reflection on the state of the art, this paper argues that more analyses of health policy in an explicitly comparative perspective are needed. This conclusion is based on a discussion of the largely unexploited benefits that could accrue from a welding of political science and health services research and a consideration of a research design illustrating the compatibility of these two endeavors.


Roles of Resolvins in Chronic Inflammatory Response.
An inflammatory response is beneficial to the organism, while an excessive uncontrolled inflammatory response can lead to the nonspecific killing of tissue cells. Therefore, promoting the resolution of inflammation is an important mechanism for protecting an organism suffering from chronic inflammatory diseases. Resolvins are a series of endogenous lipid mediums and have the functions of inhibiting a leukocyte infiltration, increasing macrophagocyte phagocytosis, regulating cytokines, and alleviating inflammatory pain. By promoting the inflammation resolution, resolvins play an irreplaceable role throughout the pathological process of some joint inflammation, neuroinflammation, vascular inflammation, and tissue inflammation. Although a large number of experiments have been conducted to study different subtypes of resolvins in different directions, the differences in the action targets between the different subtypes are rarely compared. Hence, this paper reviews the generation of resolvins, the characteristics of resolvins, and the actions of resolvins under a chronic inflammatory response and clinical translation of resolvins for the treatment of chronic inflammatory diseases.


Electrically tunable lenses - eliminating mechanical axial movements during high-speed 3D live imaging.
The successful investigation of photosensitive and dynamic biological events, such as those in a proliferating tissue or a dividing cell, requires non-intervening high-speed imaging techniques. Electrically tunable lenses (ETLs) are liquid lenses possessing shape-changing capabilities that enable rapid axial shifts of the focal plane, in turn achieving acquisition speeds within the millisecond regime. These human-eye-inspired liquid lenses can enable fast focusing and have been applied in a variety of cell biology studies. Here, we review the history, opportunities and challenges underpinning the use of cost-effective high-speed ETLs. Although other, more expensive solutions for three-dimensional imaging in the millisecond regime are available, ETLs continue to be a powerful, yet inexpensive, contender for live-cell microscopy.


Continued Increase in Melanoma Incidence across all Socioeconomic Status Groups in California, 1998-2012.
Melanoma incidence has been increasing in light-skinned populations worldwide, but the reasons for the increase have been controversial. Our prior assessment in California non-Hispanic whites showed substantial increases in invasive melanoma incidence for tumors of all thicknesses in all neighborhoods categorized by socioeconomic status (SES) between 1988-1992 and 1998-2002. To understand whether these trends continued, we updated our assessment to include the diagnosis period 2008-2012 and more accurate pathologic stage at diagnosis. We used the California Cancer Registry to calculate age-adjusted incidence rates for over 58,000 newly diagnosed melanomas. Incidence rates not only continued to rise over the 10-year period from 1998-2002 and 2008-2012 but also showed significant increases in almost all groups defined jointly by tumor thickness or stage at diagnosis and a small area (census tract) SES measure. The largest relative rate increases were seen for regional, distant, and ulcerated disease, especially among males living in the lowest SES neighborhoods. Considering tumor thickness and stage as proxies for time to screening detection and neighborhood SES as a proxy for health care access, we interpret this pattern to indicate continued, true increases in melanoma occurrence as opposed to a thin tumor phenomenon simply driven by improved access to care.


Mode of peptidoglycan synthesis in Salmonella typhimurium: single-strand insertion.
The synthesis of peptidoglycan by Salmonella typhimurium at the molecular level has been analyzed by studying the pattern of insertion of newly synthesized strands into the preexisting cell wall. We have measured the acceptor-donor radioactivity ratio during short labeling periods, and we found values between 0 and 0.2. This is less than the ratio observed by Burman and Park (Proc. Natl. Acad. Sci. USA, 81:1844-1848) for peptidoglycan synthesis in Escherichia coli. We propose that insertion of new strands occurs as single strands.


Regulation of adrenal 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase expression and activity by adrenocorticotropin and corticosterone in the rat.
This study describes the regulation of adrenal 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) expression and activity by ACTH and corticosterone, alone or in combination, in intact male and female rats as well as the effect of ACTH on 3 beta HSD expression and activity in the adrenals of hypophysectomized female animals. The effect of treatment on total 3 beta HSD mRNA levels was measured by dot blot hybridization using rat 3 beta HSD cDNA, while the specific regulation of type I and type II 3 beta HSD mRNAs was analyzed by ribonuclease protection assay. The concentration of 3 beta HSD protein was measured by Western blot, using cross-reacting antibodies raised against purified human placental 3 beta HSD, while 3 beta HSD enzymatic activity was measured by the conversion of [14C]dehydroepiandrosterone into [14C]androstenedione. The present data show that the trophic effect of ACTH on male and female rat adrenals is accompanied by increases in total 3 beta HSD mRNA, enzymatic activity, and protein content. Hypophysectomy, on the other hand, causes a marked decrease in 3 beta HSD mRNA levels and enzymatic activity, which is completely reversed by administration of ACTH. On the other hand, corticosterone treatment results in a marked inhibition of 3 beta HSD mRNA levels, enzymatic activity, and protein content in intact animals; this effect is probably mediated by a decrease in ACTH secretion. The present data show that ACTH and corticosterone, via its inhibitory action on ACTH secretion, have potent and opposite effects on the expression of two 3 beta HSD genes in the rat adrenal; a parallel effect is observed on both type I and II 3 beta HSD. Such data suggest that 3 beta HSD could well play a major role in the regulation of steroid formation in the adrenal cortex.


[Disorders of bone mineral density in patients with cholelithiasis and postcholecystectomic syndrome].
to justify the role of biliary insufficiency (BI) in the development of disorders of bone mineral density (BMD) in patients with cholelithiasis and after cholecystectomy, to introduce with main methods of diagnosis, prevention and treatment of osteoporosis and osteopenia in biliary pathology. Recent literature data showed that development of BI in the CL and PS leads to malabsorption of vitamin D and thereby contribute to the development of osteoporosis and osteopenia. The main method of diagnosis of BMD is twoenergic X-ray densitometry.


Recurrence patterns and risk factors following thoracoscopic esophagectomy with radical lymph node dissection for thoracic esophageal squamous cell carcinoma.
The aim of the present study was to clarify the therapeutic effect of thoracoscopic esophagectomy with radical lymph node dissection based on the recurrence pattern, and identify the risk factors for relapse-free survival in patients with esophageal cancer. The recurrence patterns in 140 patients who underwent complete thoracoscopic radical esophagectomy between January 2003 and December 2012 were investigated. The risk factors for recurrence were examined by univariate and multivariate analysis. Mediastinal recurrence in association with initial lymphatic metastasis was precisely analyzed. Esophageal cancer recurred in 49 (35.0%) of the 140 patients. The median recurrence time was 259 (45-2,560) days after the initial treatment. The patterns of initial recurrence among the 140 patients included hematological recurrence in 24 patients (17.1%), lymphatic recurrence in 26 (18.6%), pleural dissemination in 5 (3.6%), peritoneal dissemination in 2 (1.4%), and local recurrence in 4 (2.9%). Lymphatic recurrence within the mediastinal regional lymphatic stations occurred in only 8 (5.7%) of the 140 patients. Univariate analysis for relapse-free survival showed that the statistically significant variables were a tumor location in the upper third of the esophagus, stage of pT3 or pT4, presence of nodal metastasis, pStage of III or IV, presence of a residual tumor, performance of preoperative chemotherapy and performance of postoperative therapy. Multivariate analysis showed that only nodal metastasis and a positive residual tumor were statistically significant independent risk factors for relapse-free survival. Lymphatic recurrence within the mediastinum, particularly the station around the bilateral recurrent laryngeal nerves, was infrequent and independent of the initial metastatic distribution. Thoracoscopic esophagectomy with radical lymph node dissection provides favorable locoregional control. Lymphatic recurrence within the mediastinal regional nodes is infrequent and independent of the initial lymph node metastasis. A pathological residual tumor and lymph node metastasis are significant risk factors for recurrence.


Fetal antigens on the surface of human lymphoid cells.
Human B-lymphoblastoid cells established in long-term culture from healthy adults carry surface components that are normally found in human fetal tissues at about 10 wk of age. These antigens are strongly expressed on neoplastic B lymphocytes but not on thymocytes or a cultured T-cell line. They are carried by a small subpopulation of normal adult peripheral blood lymphocytes as well.


Characteristics, efficacy and safety testing of standardized extract of Croton tiglium seed from Indonesia as laxative material.
Identification and taxonomy analysis conducted at Herbarium Bogoriense at Research Centre for Biology, Indonesian Institute of Sciences Bogor. The name of the plant was C. tiglium L. The result of analysis on C. tiglium, ethanol extract as laxative material using the intestinal transit method showed treatment group that received dosage 0.06 mL/30 g b.wt. (72.5%) was significantly different compared to negative control (48.4%) or positive control (50.6%) which showed the weak effect as laxative at the dosage of 0.75 mL/30 g b.wt. It showed that ethanol extract of C. tiglium seed at dosage 0.06 mL/30 g is effective as laxative. The test result of the treatment using dosage 0.06, 0.04, 0.026 and 0.07 mL/28 g of body weight showed the mice population response 100, 60, 40 and 40% consecutively. The Thompson and Weil analysis result showed the ED50 was at 0.027 mL or equal to 639,5 g kg(-1) b.wt. The LD50 was at 0.0707 equals with 1674,5 mg kg(-1) b.wt. Safety limit is the range of dosage that cause the lethal effect and the dosage that gives the intended effect. The safety limit is represented by the comparison of LD50/ED50. Calculation result that the extract safety limit was LD50/ED50 = 0.0707/0.027 = 2.7.


Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe.
Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years. Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0-7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%. The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term.


Throat cultures in the office.
Office bacteriology aids clinical judgment in the diagnosis of pharyngotonsillitis and enhances quality medical care. The office bacteriology laboratory requires only a small expenditure of time and money. The technique is easily learned and is sensitive. Group A beta-hemolytic streptococci can be distinguished from other beta-hemolytic streptococci because they are readily inhibited by 0.04 u. of bacitracin.


[Use of liposomes for the association of foreign genetic material to spermatozoa].
The binding of liposomes of different composition with sperm cells and their effect on cell behaviour were studied. Experiments have demonstrated, that liposomes, containing positively charged phospholipids, had maximal degree of association with sperm cells. Besides, liposomes seem to be nontoxic for sperms and do not change the functional activity of the latter. Theoretically, sperm cells may serve as a natural vector for transfer of liposome-encapsulated DNA into the ovary cells of animals for obtaining transgenic animals.


Proteomic evaluation and validation of cathepsin D regulated proteins in macrophages exposed to Streptococcus pneumoniae.
Macrophages are central effectors of innate immune responses to bacteria. We have investigated how activation of the abundant macrophage lysosomal protease, cathepsin D, regulates the macrophage proteome during killing of Streptococcus pneumoniae. Using the cathepsin D inhibitor pepstatin A, we demonstrate that cathepsin D differentially regulates multiple targets out of 679 proteins identified and quantified by eight-plex isobaric tag for relative and absolute quantitation. Our statistical analysis identified 18 differentially expressed proteins that passed all paired t-tests (α = 0.05). This dataset was enriched for proteins regulating the mitochondrial pathway of apoptosis or inhibiting competing death programs. Five proteins were selected for further analysis. Western blotting, followed by pharmacological inhibition or genetic manipulation of cathepsin D, verified cathepsin D-dependent regulation of these proteins, after exposure to S. pneumoniae. Superoxide dismutase-2 up-regulation was temporally related to increased reactive oxygen species generation. Gelsolin, a known regulator of mitochondrial outer membrane permeabilization, was down-regulated in association with cytochrome c release from mitochondria. Eukaryotic elongation factor (eEF2), a regulator of protein translation, was also down-regulated by cathepsin D. Using absence of the negative regulator of eEF2, eEF2 kinase, we confirm that eEF2 function is required to maintain expression of the anti-apoptotic protein Mcl-1, delaying macrophage apoptosis and confirm using a murine model that maintaining eEF2 function is associated with impaired macrophage apoptosis-associated killing of Streptococcus pneumoniae. These findings demonstrate that cathepsin D regulates multiple proteins controlling the mitochondrial pathway of macrophage apoptosis or competing death processes, facilitating intracellular bacterial killing.


Cell-based screening: extracting meaning from complex data.
Unbiased discovery approaches have the potential to uncover neurobiological insights into CNS disease and lead to the development of therapies. Here, we review lessons learned from imaging-based screening approaches and recent advances in these areas, including powerful new computational tools to synthesize complex data into more useful knowledge that can reliably guide future research and development.